Coronary artery disease (CAD) is the leading cause of death in the western world. In the United States, more than 13 million people are diagnosed with CAD every year. Since its introduction in the late 1970's, Percutaneous Transluminal Coronary Angioplasty (PTCA), also known as balloon angioplasty, emerged as the principal, less invasive alternative to Coronary Artery Bypass Grafting (CABG). A limitation of PTCA is a high rate of restenosis, a condition in which the vasculature renarrows within six months of a revascularization treatment to less than 50% of its original size. Restenosis is caused by the activation and growth of vascular smooth muscle cells that make the vessel more susceptible to complete blockage. Studies have shown restenosis affects between about 25% to about 45% of PTCA patients within six months after the procedure.
Coronary stents lower restenosis rates by decreasing the vascular recoil after balloon angioplasty. A stent is a mesh-like tubular device resembling a spring that is capable of propping open a clogged artery when placed within the vessel using a specialized delivery device such as the balloon catheter used in angioplasty procedures. The stent serves as a permanent scaffolding for the newly widened vessel. Stents are percutaneous non-surgical treatments that lower the restenosis rate of PTCA by achieving a larger final luminal area. To date, stents have reduced the likelihood of acute closure after coronary revascularization procedures.
Immediately after the implantation of a stent, the healing process within the vasculature causes an overgrowth of cells and substances within and around the stent, increasing the potential for a recurrence of the blockage. The healing process leads to neointima formation which is initiated by activation of vascular smooth muscle cells, followed by emigration and proliferation with subsequent elaboration of the abundant extracellular matrix by the smooth muscle cells. As the smooth muscle cells grow on and around the stent, the vasculature renarrows and restenosis continues. Inhibition of smooth muscle cell proliferation appears to prevent the development of subsequent blockages within the vasculature as the diameter of the passageway through the vasculature is reduced by the smooth muscle cell proliferation.
Several therapeutic agents have been used in combination with stents to inhibit restenosis in the prior art. U.S. Pat. No. 6,569,195 to Yang et al. discloses a stent having a polymeric coating for controllably releasing an included active agent. The Yang et al. coating includes a blend of a first co-polymer having a first, high release rate and a second co-polymer having a second, lower release rate relative to the first release rate. U.S. Pat. No. 6,171,609 to Kunz discloses a therapeutic inhibitor of vascular smooth muscle cells. The Kunz device utilizes a cytoskeletal inhibitor and an amount of a cytostatic therapeutic agent to inhibit stenosis or reduce restenosis.
U.S. Pat. No. 6,344,035 to Chudzik et al. discloses a coating composition for use with medical devices to improve the ability of the device to release a bioactive agent in vivo. The coating composition includes the bioactive agent with a mixture of a first polymer component such as poly(butyl methacrylate) and a second polymer component such as poly(ethylene-co-vinyl acetate). The Chudzik et al. device requires the mixture of a first polymer component such as poly(butyl methacrylate) and a second polymer component such as poly (ethylene-co-vinyl acetate). In addition, the Chudzik et al. device is limited by the ability of titrating the release rate of the bioactive agent.
U.S. Pat. No. 5,788,979 to Alt et al. discloses a biodegradable coating with inhibitory properties for application to biocompatible materials. The Alt et al. device comprises a coating material comprising an anticoagulant drug wherein the coating material is adhesively applied to a surface of the biocompatible material in a substantially continuous overlying layer having a formulation, pattern and thickness selected according to a period of time in which the coating material exhibits the inhibitory action. The Alt et al. coating has shown a potential of triggering a severe vessel inflammation by activating cells after the polymer of the biodegradable coating is broken down in the vessel.
The prior art is ineffective at inhibiting restenosis and subjects patients to undesirable health risks. The prior art is limited to mixtures of specific polymer components and does not provide adequate control of the drug elution to treat a lesion. In addition, the prior art has shown a potential of triggering a severe vessel inflammation by activating cells after the polymer is broken down in the vessel. Therefore, there remains a need in the art for a method of treating a localized area of a diseased vessel after delivery of a biocompatible implantable medical device that can control the elution of the drug and is does not harm the patient.